The Genetics Core will produce knockout, mutant, and transgenic mice for each of the investigators as described in their project proposals. The Advantages of combining forces in a Core for this activity are obvious since the technical expertise required to manipulate DNA constructs, selected for homologous recombination in ES cells, and produce chimeric mice is considerable. In addition, the cost of running a mouse colony for blastocyst injection are high and the maintenance of specific Cre recombinase expressing lines in a central Core greatly reduces the cost to individual investigator and provides ready access to a valuable resource. The Genetics Core will assist all investigators by providing advice with DNA construction, ES cell culture, electroporation, selection, and screening. The Genetics Core take on the responsibility of training individuals from the participating labs in all aspects of mouse genetics and this training will occur in the Genetics Core laboratory. This hands- on guidance will assure success and encourage investigators to utilize these powerful new approaches to study cardiovascular physiology. Although it might be somewhat more efficient to simply make the mutant mice in the Genetics Core without the participation of project investigators, this was deemed to unlikely to enhance the s the training environment that we are trying to maintain as an academic entity. We expect the graduate student and postdoctoral fellows trained in our Program to be future leaders in the use of mouse genetic approaches to study cardiac function.